Urea-phosphorus compounds

ABSTRACT

where R is aryl or chloroalkyl of 2 to 10 carbon atoms, R&#39;&#39; is aryl, aryloxy or chloroalkyloxy of 2 to 10 carbon atoms, R&#39;&#39;&#39;&#39; is hydrogen, alkyl, alkenyl, furanyl or aryl of 1 to 15 carbon atoms and substituted aryl forms where the substituent is fluorine, chlorine, bromine, cyano, hydroxyl, alkyloxy, alkylthio or mixtures of such substituents, and Y is 0 or S. The organophosphorus compounds have biological activity and are also useful as fire retardants.   The present invention relates to new compounds containing urea and organophosphorus moieties in cyclic structures, to a new process for production of such compounds, and to new organophosphorus acids produced by hydrolysis of the cyclic structures.

Write States atent [1 1 51 Sept. 9, 1975 [75] Inventor:

[52] 1.1.8. Cl 260/347.2; 260/347.8; 260/465 E; 260/5025; 260/551 P;260/936; 71/86; 71/87 [51] int. Cl. C0711 105/02; C07d 5/14 [58] Fieldof Search 260/5025, 551, 936, 347.2, 260/347.8

[56] References Cited UNITED STATES PATENTS 3,673,248 6/1972 Peterson260/553 Primary Examiner-Harry I. Moatz [5 7] ABSTRACT The presentinvention relates to new compounds containing urea and organophosphorusmoieties in cyclic structures, to a new process for production of suchcompounds, and to new organophosphorus acids pro duced by hydrolysis ofthe cyclic structures.

where R is aryl or chloroalkyl of 2 to 10 carbon atoms,

R is aryl, aryloxy or chloroalkyloxy of 2 to 10 carbon atoms,

R" is hydrogen, alkyl, alkenyl, furanyl or aryl of l to 15 carbon atomsand substituted aryl forms where the substituent is fluorine, chlorine,bromine, cyano, hydroxyl, alkyloxy, alkylthio or mixtures of suchsubstituents, and

Y is O or S The organophosphorus compounds have biological activity andare also useful as fire retardants.

3 Claims, No Drawings UREA-PHOSPHORUS COMPOUNDS,

where R is aryl or chloroalkyl of 2 to 10 carbon atoms,

R is aryl, aryloxy or chloroalkyloxy of 2 to 10 carbon atoms,

R" is hydrogen, alkyl, alkenyl, furanyl or aryl of l to l5 carbon atomsand substituted aryl forms where the substituent is fluorine, chlorine,bromine, cy ano, hydroxyl, alkoxy, alkylthio or mixtures of suchsubstitucnts, and

Y is O or S.

A specific compound is 3-(2,4-dichlorophcnyl)-l,4-

dimethyl-2-phenyl l ,4,2-diazaphospholidin5-one-2 oxide which isprepared from l,3-dimethylurea, di-,

phenyl phenylphosphonite, and 2,4- dichlorobenzaldehyde according to thefollowing equation:

Whereas the cyclic product of the above equation containsthe'organophosphorus moiety in a phosphinate structure, that is, thephosphorus is bonded to two carbon atoms, when the trivalent phosphorusester reactant is a phosphite ester, the cyclic product has thephosphorus in a phosphonate structure, that is. bonded to only onecarbon atom. This is exemplified by the forl,4-dimethyl-3-(4-hydroxy-3 6mation of methoxyphenyl )-2-phenoxyl ,4,2-diazophospholidin-5-one-2-oxide from the reaction of l,3di methylurea and vanillin withtriphenyl phosphite.

The present invention also includes the free acids of the correspondingcyclic esters discussed above. These acids are produced by ring-openinghydrolysis reactions. Thus, when a cyclic ester having the phosphinatestructure is hydrolyzed, an open-chain phosphinic acid is producedaccording to the following equation:

where R is aryl of b to 10 carbon atoms, I R" is alkyl, alkenyl, furanylor aryl of l to 15 carbon atoms and substituted aryl formswhere thesubstituent is fluorine, chlorine, bromine, eyano, hy-

droxyl, alkyloxy, alkylthio or mixtures of such subistituents, and

Y is O or S. I

The use of basic materials in the hydrolysis mixture, for example diluteaqueous sodium hydroxide, may aid in the hydrolysis reaction. In suchcases the initial hydrolysis products are salts, and these can beconverted to the free phosphinic acids by acidification of thehydrolysis reaction mixture.

When cyclic esters of this invention having phosphonate structures arehydrolyzed, the products are the corresponding open-chain phosphonicacids:

R is aryl or chloroalkyl of 2 to 10 carbon atoms R is alkyl, alkenyl,furanyl or aryl of l to 15 carbon atoms and substituted aryl forms wherethe substitutent is fluorine, chlorine, bromine, cyano, hydroxyl,alltyloxy, alkylthio or mixtures of such substituents, and Y is O or S.A specific example of the phosphinic acids of this invention is A [a-( l;3-dimethylureido)-2,4- idichlorobenzyl] phenylphosphinic acid,

11 1 (HO izPc HNCON HCH,

Formation of the cyclic products of this invention is usually initiatedwhen a mixture of the three reactants, preferably in an inert solventsuch as toluene or chlorobenzene, is warmed to about 70C. The reactionis usually complete after an hour at 80-120C., but warming at higher orlower temperatures is sometimes advantageous. Gradual addition of thealdehyde reactant to a stirred mixture of the phosphorous ester and 1,3-dimethylurea reactants in a solvent at reaction temperature, usuallyfrom about 70 to 120C, may facilitate control of heat of reaction.

The cyclic products may be isolated from the reaction mixtures andpurified by standard techniques before being subjected to hydrolysis tothe corresponding acids. However, it is frequently more convenient,particularly with the cyclic phosphonates, to treat the crude,unisolated product in the reaction mixture with the required amount ofwater and then stir and warm the mixture until the desired hydrolysis iscomplete. The low solubility of the free acids in the reaction mixturesusually makes the acids easier to isolate than the parent cyclicstructures.

Specific examples showing the preparation and isolation ofrepresentative compounds of the present invention are set forthherewith, but are not limitative of the scope of the invention.

EXAMPLE 1 A solution of 0.3 mole each of diphenyl phenylphosof l and I1and appreciable differences in their nmr spectra. For 1: nmr 28.9 ppm(in CDCl;;), *38.6 ppm (in CF CO H); 'H'nmr (CDCla) 57.3 (m, 8, aryl),5.2 (d, 1, J =22Hz, PCH), 3.1 (s, 3, CH NCH), 2.9 (d, 3, J 8H2, PNCH ms370(6) (molecular ion), 368(10) (molecular ion), 335(10), 333(25),311(6), 278(23), 276( 100), 186(38), 124(43), 77(29). For 11: P nmr 25.0ppm (in CDCl;,), 32.9 ppm (in CF CO H); H nmr (CDCl 87.6 (m, 8, aryl),5.2 (d, 1, J 9H2, PCH), 2.9 (s, 3, CHNC1j 2.85 (d, 3, J 8H2, PNCH(decoupling from P converted the doublets at 5.2 'and 2.85 ppm to.singlets); ms 370(1), 368(1), 335 (12), 333(66), 311(2), 278( 13),276(100), 186(29), 124(32), 77(13).

Anal.(II) Calcd for C ,,H N Cl O P: C, 52.05; H, 4.10; CI, 19.21; N,7.59; P, 8.39. Found: C, 52.33; H, 4.14; C], 18.82; N, 7.50; P, 8.31.

EXAMPLE 2 l,4-Dimethyl-2-(4-methy1phenoxy )-3-phenyl-1 ,4,2-diazaphospholidin-5-one-2-oxide.

Benzaldehyde, 0.5 mole, is added dropwise to a solution of 0.5 mole of1,3-dimethy1urea and 0.5 mole of tris(p-t0lyl) phosphite in 100g ofbenzene as the solution was warmed from 60-90. Warming is continued atfor 3 hr, giving a reaction mixture having P nmr peaks at 24.2 and 21.9ppm (-6:1 areas). The solvent and most of the by-product p-cresol areremoved by stripping to 120/().5mm, and the remaining yellow, viscousoil is dissolved in acetone. A solid that separates is recrystallizedfrom acetone to give a white solid: mp l26.5-l28; "P nmr -24.2 ppm; Hnmr 86.9-75 (m. 9, aryl), 4.6 (d, 1, J 19Hz, PCH), 2.9 (cl, 3, J 8H2,PNCH 2.7 (s, 3, NCHa), 2.3 (s, 3, CH ms 330(50) (molecular ion), 273(1),244(4), 239(6), 223(27), 182(4), 166(100), 118(49), 107(5), 91(17),77(14), 60(42).

Anal. Calcd for C, H ,,N O P: C, 61.18; H, 5.80; N, 8.48; P, 9.38.Found: C, 61.81; H, 5.67; N, 8.33; P, 9.33.

EXAMPLE 3 l,4-Dimethyl-2,3-diphenyl-1.4,2-diazaphospholidin-5-one-2-oxide A solution-of 0.3 mole-each of bis(chloropropy1)phenylphosphonite, =1-,'3-dimethy1urea, and benzaldehyde in g of tolueneis warmed at 1 10 for 1.5 hr, giving .a light yellow reaction mixture inwhich about half of the phosphorus detectable by nmr had a chemicalshift at -25.9 ppm. Stripping to l07/0.5mm followed by dilution withether and filtration gives 14.8g of white solid: mp l32138 (l41.5-143.5from tetrahydrofuran-ether); "'P nmr -25.6 ppm; H nmr 87.3 and 7.6 (m,10, aryl), 4.6 (d, l, J=6Hz, CH), 2.9 (d, 3, J '=8Hz, CH NP), 2.8 (s, 3,Cl -l ;,NCH) (phosphorus decoupling converted both doublets tosinglets); mass spectrum .(70 eV) m/e(rel intensity) 300(27) (molecularion), 243(67), 228(35), 166(15 124(30), 118(100), 77(38), 60(15).

Anal; Calcd for C H N O P: C,- 6-398; H, 5.70; N, 9.33; I 10.31 Found:C, 63.70; H, 5.75; N, 9.06; P,

EXAMPLE 4 C H N NCH;,

A solution of 0.3 mole each of 1,3-dimethylthiourea,3,4-dichlorobenzaldehyde, and triphenyl phosphite in 75g of toluene iswarmed at 120125 for 1.25 hr, giving a yellow solution having fP nmrsignals at 27.5 and 24.7 ppm (-5:l areas). The reaction mixture isstripped to 1 /0.5mm to remove the solvent and most of the by-productphenol. Two-thirds of the resulting yellow oil is diluted with ether.kept at 5 for 12 hr and filtered, giving 352g. of white solid: mp125-126 (from butyl acetate); "P nmr 26.6 ppm; H nmr 87.2 (m, 8, aryl),4.7 (d, l, J =18Hz, CH), 3.1 (d, 3, J 7H2, CH -,NP), 3.1 (o, 3, J lHz,CH NCH); ir(KBr) 2.9(m), 6.24(w), 6.68( s), 7.20(m), 7.5 3(5), 7.87(S),837(5), l0.68,u(vs); ms 400 and 402 100) (molecular ions), 327 and329(8), 307 and 309(3), 298 and 300 (72), 186 and 188(69), 159 and161(50).

Anal. Calcd for C H Cl N O PS: C, 47,89; H, 3.77; Cl, 17.67; N, 6.98; P,7.72; S, 7.99. Found: C, 47.90; H, 3.87; Cl, 17.93;. N, 6.94; P, 7.7];S, 7.93.

The remaining one-third of the yellow oil is dissolvedin 100ml ofacetonitrile and g of H 0, and this solution is refluxed for 1 hr. Afterstanding 15 hr at room temperature, the reaction mixture is filtered,and the solid is extracted with hot acetonitrile, giving 17.8g.Recrystallization from acetic acid-water'gives l3.5g of 0:( 1,3-dimethylthioureido )-3 ,4-dichlorobenzylphosphonic acid: white solid;mp 178l79 dec; P nmr (CD SOCD3) -15.1 ppm ((1, J 24Hz): H nmr 88.5 (s,3, HO and NH), 7.7 (m, 3, aryl), 7.2(d, 1, J=24Hz, CH), 3.1 and 3.0 (s,6, CH ir(KBr) 3.02,u.(m), 3.51(m), 6.45(s), 6.78(m), 7.32(s), 790(5);acidity, 2.00 equiv/mole, pK, =3.20, pK2=8.65.

Anal. Calcd for C ,H,;,CI N O,,PS: C, 34.99; H, 3.82;

Cl, 20.66; N, 8.16; P, 9.02; S, 9.34. Found: C, 34.89;

H, 4.25; C], 20.84; N, 8.15; P, 8.81; s, 9.25. t

' EXAMPLE .5

C II O A mixture of 0.12 mole each of 4- cyanobenzaldehyde, l,3-dimethy1urea, and diphenyl phenylphosphonite in 150 m1 of toluene is warmedat reflux (1 12) for 3.5 hr and then stripped to l20/10mm, leaving aviscous, light yellow oil having P nmr peaks :at 3,1.2 and-25.7 ppm(-2:1 areas). Dilution of the oil with ether results inseparation of asolid from ,which two isomers are isolated by fractionalcrystallization. Isomer I: mp 176179; P nmr (CDCla) 30.6 ppm; H nmr 87.3(m, 9, aryl), 5.1 (d, 1,, J 22H z, PCH), 3.0 (s, 3, NCH;,),,2.9 5 (d, 3,J 8Hz, PNCH;,). isomer 11: mp l80 -l82.5; KP nmr 26 ,7 ppm; H nmr 67.8(m, 9, aryl), 4.7 (d, 1, J 7H2, PCH), 2.9 .(s, 3, NCH3), 2.9 (d, 3, J8H2, PNCH There is a sharp depression of the mixed melting point of! andII.

EXAMPLE6 2-(2-Chloroethoxy)-l,4-dimethyl 3 pheriyl-1,4,2

diazaphospholidin-5-one-2'oxide A mixture of 880g (1.0 mole) of1.3-dimethylurea, 269.5g 1.0 mole) of tris( 2-ch1oroethy1) phosphite,and

106. 1.0 mole) of benzaldeh yde is stirred under nitrogen and warmed atl03106'for 3.5 hr, giving a light yellowsolution: P nmr 139.0, 28.3,22.8 (area ratio 1 :'8:2). The by product ethylenechlorohy' drin isstripped off to ?/O.1mm, and ml of henzene is added. Solid separates asthe reaction mixture cools. Recrystallization from acetonitrile gives50.1g, mp l34135'.'5. A second recrystallization from acetonitrile givesa white solidzmp 136-137; P nmr 28.5 ppm; H mm 57.3 (m, 5, aryl') 4.6(01, 1,1: 19Hz, CH), 4.3 (m, 2,061, 3'.7' m, 2,CH Cl), 2.9 (d, 3.1: 8H2,P cH-J; 2.8 (s, 3, CH NCl1-1j; ir(l Br)"3.42, m), 5.78(s'), 6.90(m),7.22(in)', 7,95(vs); mass spectrum (70 eV) m/e (rel intensity) 3"02( 26)(molecular ion), 273(2), 245(9), 239(4()), 216(6), 182(8), 166(5),118("10()),9l(14).

Analycalcd for CI2H1HCINEO3PI C, 47.61;;H, 5.33; C1, 11.71; N, 9.25; P,10.23. FoundrC, 47.69; H, 5.25; CI, 11.69; N,9.34; P, 10 .38.

The filtrates'are combined and treated-with 30g of water at reflux for0.5 hr; Filtration of the warm reaction'mixtur e and then extraction ofthe solid with warm acetonitrile gives 50.9g of a-(1-3-dirnethyl ureido)ben- .zylphosphonic acid; 178 -180 dec; P nmr (CD,;SOCD -;)18.2 ppm; H510.1 (broad, 3, HO and NH), 7.3 (m, 5', aryl), 5.8 (d, '1, J 24Hz, CH),2.9 (S,

EXAMPLE 7 1.4-Dimcthyl-3-( 4-hydroxy-3-methoxyphenyl )-2- phenoxy- 1,4,2-diazaphospholidin-5-one2oxide A mixture of 76. lg (0.5r'n'ole)ofvani11in,44.0g (0.5 mole) of 1,3-dimethylurea, and 155.0g (0.5 mole)of triphenyl phosphite in 200g of benzene is stirred und'er N and warmedat reflux (95) for 1 hr. About half of the benzene is distilled to givea yellow solution: P

EXAMPLE 8 a-( 1,3-Dimcthylureido)benzylphosphonic acid.

mixture of 155.2g (0.5 mole) of freshly distilled triphenyl phosphite53.0g (0.5 mole) of benzaldehyde, and 44.1g (0.5 mo1e) ofl,3-dimethylurea in 150g of toluene is stirred under N and warmed. Heatof reaction is noticeable at -80, and cooling is used for -10 minutes tokeep the temperature below 85. The reaction mixture is warmed at reflux1 17) for 1.25 hr and then stripped to 140/0.15mm to give crude 1,4-dimethyl 3-phenyl-2-phenoxy-1,4,2-diazaphospholidim-S-one-oxide whichsolidifies when cooled, nmr 24.4, 21.9, and -20.0 ppm (-8: 1:1 areas),Acetonitrile (150ml) and 360g (2.0 moles) of distilled water are added,and the solution is warmed at reflux for several hours. Solid that formsduring warming is separated by filtration of the hot reaction mixture,giving 104.5g (80.9% yield), mp 178181 (with foaming). Recrystallizationof a portion from isopropylalcohol gives a white solid: mp l81 182 (withfoaming); ""P nmr (DMSO- 18.1 ppm (d, .1 24Hz); H nmr 89.6 (broadsinglet, 3, OH and NH), 7.3 (m, 5, C ,;H 5.7 (d, 1,.l,, 24Hz), 2.9 (s,3, NCHa), 2.6 (s, 3NCH;,); acidity, 2.01 equiv/mole, pK 2.20, pK 8.62.

Anal. Calcd for C,,,H ,,N O P: C, 46.51; H, 5.85; N, 10.85; P, 11.99.Found: c, 46.60; H 5.78; N, 10.79; P, 12.10.

Phenol, 109.9g (78% yield), is 'isolatedfrom the distillate andfiltrate.

EXAMPLE 9 V 1-( 1,3-Dimethylureido)-2-ethy1hexy1phosphonic acid.

11 (HO).7,PCHNCON1-1CH;,

A mixture of 88.1-g (1.0 mole) 0f 1 ,3-dimethy1urea, 269.5g 1.0 mole) oftris(2-ch1oroethyl) phosphite, and 1 35g.( 1.05 moles) of2-ethy1hexaldehyde is warmed at l051 10 for 2 hr, giving a clearcolorless solution: nmr 30.8 and 28.2 ppm (-2:1 areas). Four-fifths ofthe reaction mixture is dissolved in' 200ml of cyclohexane containing34.5g of H 0, and the mixture is warmed at 82 for 0.5 hr. Filtrationafter cooling, and extraction of the solid with hot acetonitrile gives54.7g of white solid 100.8g more separates from the filtrate whilestanding); mp 184186 dec; "P nmr (CD SOCD 23.5 ppm(m); H nmr 89.8(broad, 2, 0g), 4.4 1 of d, 1,1 10 and 20112, PCH), 2.7 (s, 3, NCH.-;),2.5 (s, 3, NCH 0.5-2.0 (broad, l5, hexyl); acidity 1.985 equiv/mole, pK1.76, pK- 5.29.

Anal. Calcd for C H -,N O P: C, 47.13; H, 8.99; N, 9.99; P, 11.05.Found: C, 47.41; H, 9.59; N, 10.03; P, 1 1.34.

EXAMPLE-'10 a( 1,3-Dimethy1ureido )-4-hydroxy-3-methoxybenzylphosphonicacid.

I EXAMPLE 1 1 1-( 1 ,3-Dimethylureido )-3-( methylthio )propylphosphonicacid 1 I 0 (H;, I

1110 )-I .IIICHNC(V)NHCH;,

(H CH SCH When a mixture of 0.5 mole each of 1.3-

dimethylurezntriphenyl phosphite, and 3-methy1thiopropionaldehyde in gof toluene is warmed to 75, a reaction is initiated and the temperatureincreases rapidly to 120. After further warming at for 1 hr, theresulting yellow solution has a '1? nmr signal only at 28.2 ppm. Afterthe solventand most of the byproduct phenol are removed by stripping to1 10/1mm. one-third of the residue is dissolved in 75ml of acetonitrileand 10g of water, and this solution is refluxed for 3 hr. The reactionmixture is allowed to evaporate to dryness, and the residue is extractedwith ether and then with hot acetonitrile and recrystallized twice fromacetic acid to give a white solid: mp 164.5-167; P nmr (DMSO-d 21.4 ppm;H nmr 69.6 (broad, 2, OH), 4.5 (m, 1, PCH), 2.8 (s, NCHK), 2.0 (s,SCH,,), 1.9-2.6 (m, cfl Clj S).

' EXAMPLE '12 l-( 1,3-Dimethy1ureido )3,7-dimethylocta-2,6-dienyl- Vl-phosphonic acid A mixture of 44.0g (0.5 mole) of 1.3-dimethylurea,

135g (0.5 mole) of tris( 2ch1oroethy1) phosphite, and

76.1g (0.5 mole) of citral is warmed at 95105 for 3.75 hr. Water, 54g(3.0 moles), is added, and warming is continued at 7590 for 1 hr more.The reaction mixture is diluted with 200ml of acetonitrile and al lowedto stand at room temperature for 12 hr. Solid that forms is extractedtwice with hot acetonitrile, giving 17.6g, mp l55-l57 dec.Recrystallization from acetic acid gives a white solid: mp 157159 dec; P(CD SOCD 2().8 ppm (m); acidity 1.97 equiv/mole, pK 3.85, pK 9.29.

Anal. Calcd for C ;,H -,N O ,P: C, 51.29; H, 8.28; N, 9.20; P, 10.18.Found: C, 51.03; H, 8.75; N, 9.05; P,

EXAMPLE 13 [a-( 1,3-Dimethylureido )-2,4-dichlorobenzyllphcnylphosphinic acid A suspension of 14.4g (0.039m) ofdichlorophenyl)-l,4-dimethyl-2phenyl-1,4,2-diazaphospholidin-5-one-2-oxide in 120ml of ethanol is stirred as 0.04mof NaOH 1.0 molar solution) is added dropwise. The solid startingmaterial goes into solution and then another solid separates after a fewminutes. This is separated by suction filtration, washed with ethanol,and then extracted. with hot acetonitrile to give the sodium salt, awhite solid, mp -294 dec.; P nmr (D 25.8 ppm; H nmr 57.()8. 15 (m, 8,aryl), 5.8 (d, 1, J 14Hz, PCH), 3.0 (s. 3, NCH3), 2.6 (s, 3, NCH Asolution of 8.5g of this salt in 200 ml of H 0 is stirred as 5g oftrifluoroacetic acid is added dropwise.

Solid separates immediately. It is recrystallized from acetonitrile togive a white solid, mp 178; P nmr (DMSO-d "31 .7 ppm; H nmr 87-85 (m, 8,aryl 6.1

(d, 1, J =14HZ, PCH), 2.9 (S, 3. NCHs). 2.5 (S. 3.

NCH acidity 0.98 equiv/mole,pK,, 4.12.

Anal. Calcd for C ,,H Cl N O P: C, 49.63; Cl, 18.31; N, 7.23; P, 8.00Found: C, 49.72; H, 4.49; Cl, 18.58; N, 7.29; P, 8.12.

EXAMPLE 14 1 ,4-Dimethy1-3-(2-furanyl)-2-phenoxy-1,4,2-diazaphospholidin-5-one-2-oxide Under conditions similar to those usedfor the preparation of Example 7 except that furfural is used as thealdehyde reactant, the subject compound is obtained as a white solid: mp129 131"; P nmr c130, 20.9 ppm; H 66.47.4 (m, 8, aryl), 4.8 (d, 1, .120Hz, CH), 3.0 (d, 3, J 32 8H2, CH NP), 2.8 S, 3, CH,,NCH); ms m/e 330629) molecular ion, 213(6), 156( 108( 24).

EXAMPLE 15 When a portion of the product of Example 14 is dissolved inacetonitrile and the solution is treated with water and warmed, v1,3-dimethylureido) (2-furanyl)methylphosphonic acid is produced.

EXAMPLE" l6 l,4-Dimethyl-2-phenyl-1,4,2-diazaphospholidin-5-thione-Z-oxide A mixture of 312g (0.3 I mole) of 1,3-dimethyltl'iiourea, 883g (0.3 mole) of diphenyl phenylphosphonite and gof paraformaldehyde in 80g of toluene is stirred under N and warmed atreflux for 3 hr.A1ter standing overnight, the reaction mixtureisfiltcred to remove a srnall amount of solid, and the filtrate isstripped to 120/0.2mm. The residue is extracted twice with ether andonce with cyclohexane, and the remaining insoluble material isrecrystallized twice from acetonitrile to give 32g (44% yield) of whitesolid: mp -172; "P nmr 3 1 .5 ppm; H nmr 87.6 (m, 5,

8.2Hz, HCl l), 3.4 (d, 3, J =1.2Hz, CH NCH:1). 3.0 (d, 3, J 7.2Hz, PNCHms240 (molecular ion).

Anal. Calcd for C H N OPS: C, 49.98; H, 5.45; N, 11.66; P, 12.89; S,13.34. Found: C, 50.00; H, 5.33; N, 11.67; P, 12.92; 5, 13.20.

EXAMPLE 17' 1,3-Dimethylthioureidomethyl )phenylphosphinic acid Amixture of 1,4-dimethyl-2-phenyl-l ,4,2-diazaphospholidin-5-thione-2-oxide and 40ml of ethanol is stirred as0.035m of NaOH (l molar solution) is added dropwise. Solid dissolvesduring the NaOH addition. The reaction mixture is allowed to evaporateto dryness, and the residue is washed with ether to give crude sodiumsalt, a white solid: mp 242260; P nmr (D 0) 24.7 ppm; H nmr 87.2 (m, 5,C H 3.9 (d, 2, J 8H2, CH 3.0 (s, 3, CH 2,9 (s, 3. CH A 5.0g portion isdissolved in 80 ml of distilled water, and the solution is stirred as2.2g of trifluoroaeetic acid is added dropwise. A white solid thatseparates after a few minutes is recrystallized from acetonitrile: mpl61163; 'P nmr (DMSO-d 31.2 ppm; H nmr 87.3 8.4 (m, 6, C,;H,-, and OH),4.3 (d, 2, J 7H2, CH 3.1 (s, 3, CH 2.9 s, 3, CH acidity 0.990equiv/mole, pKa 4.05. a

EXAMPLE 1 8 1,4-Dimethyl-2-phenoxy-l ,4,2-diazaphospholidin-- one2-oxideCHHN NCH" C ll 0 A mixture of 220g (0.25 mole) of 1,3-dimethylurea, 8.6gof paraformaldehyde, and 77.5g (0.25 mole) of triphenyl phosphite in100g of benzene is warmed to 80 where heat of reaction is evident, andcooling is needed for a few minutes to keep the temperature below 84.The reaction mixture is warmed at reflux for 1 hr and then stripped to105/0.5mm to remove solvent and part of the by-product phenol. Solidthat separates upon cooling is isolated by filtration and thenrecrystallized 3 times from diglyme to give 23.2g of white solid: 'mp124l28; P nmr -23.4 ppm; H nmr 67.2 (m, 5, aryl), 3.6 '(d, 2, J =Hz, CH2.9 (d, 3, J 8H2 CH NP), 2.9 (d, 3, J lHz, CH NCH (decoupling fromphosphorus converts all three doublets to singlets); mass spectrum (70eV) m/e (rel intensity) 240(63) (molecular ion), 211 (2), 183(1),147(12), 140(99), 90(10()), 56(5), 47(23), 42(86).

Anal. Calcd for C H N Q-fz C, 50.00; H. 5.46; N, 11.66; P, 12.89. Found:C, 49.98; H, 5.63; N. 11.63; P, 12.70.

EXAMPLE 19 1 1,3-Dimethylureido )methylphosphonic acid A solution of120g (0.05 mole) of the product of Example 18 in g of acetonitrile and10g of water is refluxed for 1 hr. Solid that separates upon cooling isstirred in boiling aeetonitrile, and the mixture is filtered while hotto give 7.4g (827:) of white solid: mp 168,l69 (dee.); 'P nmr (CD SOCD20.0 ppm; N nmr89.5 (broad, '-3, HO and HN), 3.5 (d, 2, J 10Hz, CH 2.9(s, 3, CH 2.6 (s, 3, CH

Anal. Caled for C H N O P: 26.38; H, 6.09; N, 15.38; P, 17.01. Found: C,26.54; H, 6.16; N, 15.27; P, 17.17.

This phosphonic acid is prepared in a similar manner usingtris(2-ehloroethyl) phosphite as the phosphorus ester reactant. Thecrude intermediate 1,4-dimethyl-2- (2-chloroethoxy) l,4,2-diazaphospholidin-5-one-2- oxide (P nmr -24.9 ppm is hydrolyzedwithout isolation from the reaction mixture to give the acid: mp 171l72dec (acetic acid-water).

EXAMPLE 20 l ,4-Dimethy1-3-(4-bromo-2-fluorphenyl )-2-( 2 naphthy1)-l,4,2-diazaphospholidin-5one-2-oxide When an equimolar mixture ofdiphenyl2-napthylphosphonite, 4-bromo-2-fluorobenzaldehyde and 1,3- dimethylureain toluene is warmed at reflux for one hour, followed by cooling in anice bath, a white solid product forms. A portion of this solid isdissolved in ethanol and an equivalent amount of sodium hydroxide 1Omolar solution) is added dropwise to the stirred solution. The reactionmixture is allowed to evaporate to dryness, and-the residue is washedwith ether, giving a crude sodium phosphin'ate salt. This salt isstirred in distilled water as slightly more than one equivalent oftrifluoroacetic acid is added. The product is separated by filtrationand then washed with water and recrystallized, giving [a-(l,3-dimethylureido)-4-bromo-2- fluorobenzyl ]2-naphthylphosphinic acid.

The nitrogen-containing organophosphorus compounds of the presentinvention are useful as biological toxicants. The following examplesillustrate the use of typical products.

Pre-emergent herbicidal activity of representative compounds of thisinvention is determined by the following procedure:

A good grade of top soil is placed in aluminum pans and compacted to adepth of three-eighths to one-half inch from the top of the pan. Apro-determined number of seeds of each of several plant species areplaced on top of the soil in'the pans. The seeds are covered with soiland the pans leveled. The herbicidal composition is applied by sprayingthe surface of the top layer of soil with a solution containing asufficient amount of active ingredient to obtain a rate of applicationof 10 lbs. per

aree. The pans are then placed on a sand bench in the greenhouse andwatered from below as needed. The plants are observed at the end ofapproximately 14 days and the results recordedf 1 13 Pro-emergentactivity of the compounds prepared in the designated Examples isobserved against the species as shown in the table below, wherein Xdenotes that herbicidal activity is observed.

PRE-EMERGENT TESTING Compound of Example 3 4 l2 l4 General Nzirruwleul'General Broudlenf Canada Thistle Cocklehur Velvetleaf Morning GloryLamhsquarters Smartwecd Ouaekgrass Johnsongrass Downy BromcBarnyardgrass What is claimed is: 1. Process for the preparation ofwhere R is selected from the group consisting of phenyl, tolyloxy,chloroethoxy, phenoxy, and naphthyl, R

is selected from the group consisting of hydrogen,

fury], alkyl or alkenyl of l to 15 carbon atoms, phenyl, and phenylsubstituted with chlorine, bromine, fluorine, cyano, hydroxy or methoxy,and Y is O or S, which comprises heating CH NHC(Y)NHCH3. R"CHO and (RO)PR in an inert solvent where R is aryl or chloroalkyl of 2 to 10 carbonatoms. 2. Process for the preparation of C ll ROP-CHR -Continued where Ris selected from the group consisting of phenyl and 1 tolyl, andchloroethoxy R is selected from the group consisting of hydrogen, fury],alkyl or alkenyl of l to 15 carbon atoms, phenyl, and phenyl substitutedwith chlorine, bromine, fluorine, cyano, hydroxy or methoxy, and Y is Oor S, which comprises CH;,NHC(Y)NHCH;,IRCHO and (RO) P in an inertsolvent where R is selected from the group consisting of phenyl, tolyland chloroethoxy.

. Page 1 of 2 UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTIONPatent No. 5,90 +,65 Dated September 9, 1975 lnven fl Gail H. Birum Itis certified that error appears in the above-identified patent and thatsaid Letters Patent are hereby corrected as shown below: Q

Column 2, the equation, lines *8-55 should read:

ROP CHR" O R Y H I H CH N NCH' H0) P-CHNCNHCH ROH 3 3 2 3 c CH n YColumn 5, line H0 should read: -3.l

Column 8, line +1 shouldread methoxyphenyl)-2phenoxy-l,H,2diazaphospholidin--5-one-2-,

In column 10, line 25 should read 306(29).

Page 2 of 2 UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION PatentNo. 5,9O +,65L+ Dated September 9, 1975 Inventor(s) Gail Birum It iscertified that error appears in the above-identified patent and thatsaid Letters Patent are hereby corrected as shown below:

In column 11, Example 17,-top equation, S should be double bonded to Cas per below:

H H C H P"CH 1 TCNHCH OH CH Signed and Scaled this Fourteenth D3) OfJune 1977 [SEAL] Arrest:

RUTH C. MASON C. MARSHALL DANN Arresting Officer Commissioner nflarenrsand Trademarks

1. PROCESS FOR THE PREPARATION OF
 2. Process for the preparation of 3.Process for the preparation of